Risk of hospitalization resulting from upper gastrointestinal bleeding among patients taking corticosteroids: a register-based cohort study.

PURPOSE: We assessed the risk of hospitalization for upper gastrointestinal bleeding among patients using systemic corticosteroids, accounting for the use of other drugs that may increase the risk of bleeding. SUBJECTS AND METHODS: We conducted a population-based cohort study in North Jutland County, Denmark. Data on the use of corticosteroids, nonsteroidal anti-inflammatory drugs, aspirin, and anticoagulants during 1991 to 1995 were obtained from a countywide prescription database. All hospitalizations because of upper gastrointestinal bleeding were identified through the Hospital Discharge Registry. The observed numbers of patients with gastrointestinal bleeding in various exposure categories among corticosteroid users were compared with the expected number based on the North Jutland population who did not receive prescriptions for any of the drugs under study. RESULTS: A total of 45,980 patients accrued 18,379 person-years of corticosteroid use. There were 109 hospital admissions for gastrointestinal bleeding among corticosteroid users, compared with 26 expected, yielding a relative risk of 4.2 [95% confidence interval (CI): 3.4 to 5.0]. Among corticosteroid users who did not use other drugs associated with gastrointestinal bleeding, the relative risk was 2.9 (95% CI: 2.2 to 3.7). The relative risk decreased further to 1.9 (95% CI: 1.4 to 2.5) when current corticosteroid usage was compared with former usage. CONCLUSION: We observed an increased risk of hospitalization because of upper gastrointestinal bleeding among patients prescribed corticosteroids, especially among those who use other medications. Confounding from the underlying disease may also have contributed to the observed increase in risk.

The safety of proton pump inhibitors in pregnancy.

AIM: To assess the safety of proton pump inhibitors during pregnancy. METHODS: Fifty-one pregnant women exposed to proton pump inhibitors around the time of conception or during pregnancy were compared with 13 327 controls without exposure to any prescribed drug in a population-based study based on The Pharmaco-Epidemiological Prescription Database of North Jutland and the Danish Hospital Discharge Registry. RESULTS: Three babies with malformations were found among 38 women exposed to proton pump inhibitors from 30 days before conception to the end of the first trimester. No cases of stillbirth were recorded. Crude relative risks of malformation, low birth weight and preterm delivery were 1.6 (95% CI: 0.5-5.1), 1.8 (95% CI: 0.2-13.0) and 2.3 (95% CI: 0.9-6.0), respectively. CONCLUSIONS: In this population-based follow-up study, we found no substantially elevated risk in terms of malformations, low birth weight or number of preterm deliveries in pregnancies exposed to proton pump inhibitors. However, further monitoring is warranted in order to establish or rule out a potential association between the use of proton pump inhibitors and increased risk of either cardiac malformations or preterm birth.

Characterisation of Liver membrane autoantibodies determined by indirect immunofluorescence.

Indirect immunofluorescence studies were performed using sera and IgG-Fab2 fragments from patients with chronic active hepatitis (CAH) who were positive for a liver membrane antibody (LMA). The specificity was investigated using hepatocytes from humans as well as rabbit, rat, guinea pig and monkey. Only sera also positive for smooth muscle antibody gave staining of lymphocytes and absorption with F-actin from rabbit muscle abolished this as well as all other smooth muscle staining without influencing LMA. It was concluded that LMA, routinely detected by indirect immunofluorescence using rabbit hepatocytes, represents specific binding to non-species-specific membrane antigens which are normal constituents of human hepatocytes. The antigen is separately located, and not cross-reactive with F-actin.

Localisation of immunoglobulin on the liver cell surface in primary biliary cirrhosis.

Direct immunofluorescence studies were performed on isolated liver cells in order to detect surface localisation of IgG in acute and chronic hepatitis and primary biliary cirrhosis. Membrane-bound IgG was demonstrated in nine patients. Six of eight patients with primary biliary cirrhosis showed granular fluorescence on their liver cell surfaces suggesting that an antibody or immune complex-mediated cytotoxicity might be involved in the pathogenesis of this disease.

Prevalence of hepatitis B virus infection among alcoholic patients with liver disease.

The aim of this investigation was to elucidate a possible role of hepatitis B virus (HBV) in the pathogenesis of liver diseases in alcoholics. Two hundred and fifty-three alcoholics with liver disease were admitted to two medical departments in Copenhagen during a 15 months period. Seventy-nine patients (31%) showed serological signs (HBsAg, anti-HBs) of previous or active HBV infection. This is a significantly higher prevalence than found in an age-matched control population. Among the 79 patients with HBV markers, a total of 11 was found to be HBsAg-positive. From these 11 patients liver specimens were available for re-evaluation in nine cases. In only three of these liver biopsies, morphological changes indicating alcohol as the aetiological cause were found. In conclusion, different or concomitant aetiology must be considered in alcoholics with liver disease.

[Transmission of hepatitis B from an adopted child to an adult]. / Hepatitis B-smitte fra et adoptivbarn til en voksen.

A case of acute hepatitis B infection in a 43 year-old male is presented. Seven months before admission the family had adopted a two year-old boy from India, and the child was later found to be seropositive for HBsAg. The patient had no other risk factors of hepatitis B infection and transmission of hepatitis B virus from the adopted child is suspected. It is recommended that children who are adopted from countries with high hepatitis B virus prevalence should be examined for HBsAg, and adoptive family members be vaccinated if the child is found to be HBsAg seropositive.

[Autoimmune hepatitis. Forms of manifestation, diagnosis and treatment]. / Autoimmun hepatitis. Fremtroedelsesformer, diagnostik og behandling.

A retrospective study concerning ten patients with autoimmune hepatitis (AiH), diagnosed during a 2 1/2-year period is presented. The age of the patients ranged from 25 to 82 years and nine of the patients were women. Their symptoms included jaundice, pruritus, fever, anorexia and fatigue during a few weeks to years. Seven patients had increased serum aspartate aminotransferase (ASAT) levels. The three patients with normal ASAT levels had hypoalbuminaemia, decreased level of prothrombin or high levels of serum immunoglobulin G. Moderate or high levels of smooth muscle antibody titer were detected in nine patients, while none had increased levels of anti-nuclear antibody titer. Histological features of moderate or severe chronic active hepatitis were demonstrated in nine patients. One patient presented with clinical and histological features of acute hepatitis. Prednisolone therapy was followed by biochemical improvement in all the patients. In one patient, maintenance therapy with prednisolone was combined with azathioprine.

[Primary sclerosing cholangitis]. / Primaer skleroserende cholangitis.

Primary sclerosing cholangitis (PSC) is an uncommon disorder of unknown etiology, characterized by chronic inflammation and fibrosis of the intra- and extrahepatic bile ducts. PSC is commonly associated with chronic inflammatory bowel disease, especially ulcerative colitis, and often in younger men with an extensive colitis. The diagnosis is made by endoscopic retrograde cholangiography. The characteristic findings are multiple strictures and dilatations of the intra- and extrahepatic bile ducts. Patients with PSC usually have a cholestatic biochemical profile. The liver biopsy findings are often non-specific. Different survivals in these patients have been described. However, asymptomatic patients seems to have a more favorable prognosis. The only curative treatment is liver transplantation.

[Recommendations for treatment of paracetamol poisoning. Danish Medical Society, Study of the Liver]. / Rekommandation for behandling af paracetamolforgiftning.

Based on recent reports concerning the efficacy of N-acetylcysteine (NAC) in paracetamol (acetaminophen) poisoning, guidelines for treatment and control of these patients are reviewed by a study group under the Danish Association for the Study of the Liver. It is recommended that NAC-treatment is initiated immediately after referral and continued for 36 hours in all cases. Further NAC-treatment should not be discontinued before a decrease in INR has been observed.

[Detection of cholangiocarcinoma in primary sclerosing cholangitis by positron emission tomography]. / Detektion af kolangiokarcinom ved primaer skleroserende cholangitis ved hjaelp af positron-emissionstomografi.

Primary sclerosing cholangitis (PSC) predisposes to cholangiocarcinoma (CC). PET scanning can assess metabolism in vivo. The glucose analogue [18 F]fluoro-2-deoxy-D-glucose (FDG) accumulates in malignant tumours because of high glucose metabolism. PET scanning of the liver was performed after intravenous FDG in nine patients with PSC, six with PSC + CC, and five controls. "Hot spots" with radioactivity accumulation were seen in each PSC + CC patient, but not in the two other groups. Values of net metabolic clearance of FDG, K (ml min-1 100 ml-1 tissue), was in CC hot spots 1.59 to 4.17 (median, 2.34; n = 6); in reference liver tissues of these patients 0.40 to 0.69 (0.49); in PSC 0.23 to 0.53 (0.36); in controls 0.20 to 0.34 (0.31). The difference between K in CC hot spots and the other groups was statistically significant (P < 0.001). FDG-PET may detect small CC tumours and be useful in therapeutic management of PSC.

[Sclerosing cholangitis and ulcerative colitis. Regional prevalence]. / Skleroserende cholangitis og colitis ulcerosa. Et regionalt materiale.

The aim of the study was to determine the prevalence of primary sclerosing cholangitis (PSC) in a regional population of patients with ulcerative colitis (UC). Three hundred and five patients with UC followed over a 12 year period were examined for elevations of serum alkaline phosphatase (> 280 U/l). Twenty four such patients were found. If no cause of these elevations were found by initial investigations, endoscopic retrograde cholangiography was performed in order to determine whether they had PSC. Eleven patients were found to have PSC (3.6%), of whom five had progressive disease, including two deaths from cholangio-carcinoma, during a six-year observation period. We found no certain relation between the extent, duration or activity of ulcerative colitis and the presence of PSC. Alkaline phosphatases were elevated up to 3.7 times the upper reference level, the aminotransferases were only found to be mildly elevated.

[Euricterus. A European database on icterus with emphasis on the Danish contribution]. / Euricterus. En europaeisk icterusdatabase med fokus på den danske andel.

Clinical and biochemical data were collected prospectively from 8032 jaundiced patients to form a database as part of a EU-supported project on computer-aided diagnosis. Patients were recruited prospectively from centres in all EU-countries and some other countries as well. Five hundred and twenty-eight jaundiced patients were collected from four centres in Denmark. Alcoholic cirrhosis, acute alcoholic liver disease and malignancy of the pancreas or the biliary tract were more common in the Danish data base: 49% of cases in Denmark as compared to 30% of cases in the international database. Viral hepatitis was underrepresented in Denmark, 16% as compared to 23% in the international group. A crude Bayesian diagnostic programme on the total database with 17 diagnostic groups achieved 63% accuracy. For the 528 Danish cases the diagnostic accuracy was 64% when the European data base was used, whereas it increased to 81% when only the Danish data base was taken as basis for the calculations. In conclusion, we found a drop in diagnostic accuracy for the Danish patients when using the large European data base instead of the national one.

Autoantibodies and immunoglobulins in alcoholic steatosis and cirrhosis.

Antinuclear antibodies were significantly more prevalent (p less than 0.01) in 143 patients with alcoholic cirrhosis than in 64 patients with alcoholic steatosis and in 94 controls. Smooth muscle antibodies were significantly more prevalent (p less than 0.05) in patients with alcoholic steatosis and cirrhosis than in controls. The prevalence of antimitochondrial antibodies and IgG liver membrane antibodies did not differ significantly between the three groups. Immunoglobulin G, A, and M concentrations were only occasionally increased in patients with steatosis. Patients with cirrhosis had significantly increased (p less than 0.005) concentrations of immunoglobulins G, A, and M when compared to patients with steatosis. These results indicate that the degree of liver damage has more effect than chronic alcoholism on the humoral immune system. Whether this influence is direct or indirect remains to be established.

Auto-antibodies in Sjögren's syndrome. With special reference to liver-cell membrane antibody (LMA).

Sera from 70 patients with Sjogren's syndrome (SS), of whom 40 had primary and 30 secondary SS, were tested for various auto-antibodies of the IgG, IgA and IgM classes. 20% had liver-cell-membrane antibody (LMA), 90% had anti-nuclear antibodies (ANA), 40% salivary-gland antibodies (SGA), 13% anti-mitochondrial antibodies (AMA), 33% smooth-muscle cell antibodies (SMA), 9% skeletal-muscle antibodies (SKA) and only 1% had parietal-cell antibodies (PCA). In addition, 53% had IgM rheumatoid factor and 6 patients with anti-DNA antibodies all had SLE. 64% had increased serum IgG, 24% IgA and 14% IgM. A significantly higher incidence of ANA was found within all three Ig classes in patients with secondary SS. AMA and IgM-rheumatoid factor were also found to be elevated in this group. On the other hand, SGA occurred most frequently in patients with primary SS. LMA was mainly of the IgG class and IgG AMA and SMA were more often present in these patients than in those with a negative LMA reaction. The results of the investigation suggest inter alia that inflammatory liver disease, although not indicated by either the case history, physical examination or biochemical values, is probably present in patients with SS.

Circulating immune complexes involving autoantibodies in chronic active hepatitis.

The mere presence of circulating immune complexes has been extensively reported in inflammatory liver diseases. In the present study, immune complexes were determined in 6 patients with HBsAg-negative chronic active hepatitis by sucrose density gradient ultracentrifugation. If present they were characterized concerning size and possible autoantibody-specificity. In four of these patients, zonal profiles differed markedly from normal controls and high molecular weight IgG-reactive substances with specificity against nuclear, smooth muscle and liver membrane antigens were demonstrated. Two patients were investigated repeatedly during one year of prednisone therapy and complex levels and size decreased along with clinical and biochemical improvement. Also in four positive controls with active SLE, complexes of up to 38 S containing antinuclear antibodies were detected. In contrast to patients with chronic hepatitis, SLE patients all had normal levels of serum gammaglobulin. It was concluded that immune complexes, present in liver disease without systemic organ-involvement and containing autoantibodies, might possibly reflect the normal immune clearance.